Genetics of Nonalcoholic Fatty Liver Disease: A 2018 Update

Nonalcoholic fatty liver disease (NAFLD), now the leading cause of liver damage worldwide, is epidemiologically associated with obesity, insulin resistance and type 2 diabetes, and is a potentially progressive condition to advanced liver fibrosis and hepatocellular carcinoma. However, there is huge interindividual variability in liver disease susceptibility. Inherited factors also play an important role in determining disease predisposition. During the last years, common variants in PNPLA3, TM6SF2, MBOAT7 and GCKR have been demonstrated to predispose to the full spectrum of NAFLD pathology by facilitating hepatic fat accumulation in the presence of environmental triggers. Other variants regulating inflammation and fibrogenesis then modulate liver disease progression in those at higher risk. Evidence is also accumulating that rare variants are involved in disease predisposition. In the future, evaluation of genetic risk factors may be exploited to stratify the risk of liver-related complications of the disease, and to guide hepatocellular carcinoma surveillance and choose pharmacological therapy.